C A S E R E P O R T Open AccessRhodococcus equi venous catheter infection: a case report and review of the literature Rosalinda Guerrero1, Ashish Bhargava2and Zeina Nahleh1* Abstract Int
Trang 1C A S E R E P O R T Open Access
Rhodococcus equi venous catheter infection:
a case report and review of the literature
Rosalinda Guerrero1, Ashish Bhargava2and Zeina Nahleh1*
Abstract
Introduction: Rhodococcus equi is an animal pathogen that was initially isolated from horses and is being
increasingly reported as a cause of infection in humans with impaired cellular immunity However, this pathogen is underestimated as a challenging antagonist and is frequently considered to be a mere contaminant despite the potential for life-threatening infections Most case reports have occurred in immunocompromised patients who have received organ transplants (for example kidney, heart, bone marrow) or those with human immunodeficiency virus infection Infections often manifest as pulmonary involvement or soft tissue abscesses Bacteremia related to
R equi infections of tunneled central venous catheters has rarely been described
Case presentation: We report the case of a 63-year-old non-transplant recipient, non-HIV infected Caucasian woman with endometrial carcinoma who developed recurrent bloodstream infections and septic shock due to R equi and ultimately required the removal of her port catheter, a subcutaneous implantable central venous catheter
We also review the medical literature related to human infections with R equi
Conclusion: R equi should be considered a serious pathogen, not a contaminant, particularly in an
immunocompromised patient who presents with a central venous catheter-related bloodstream infection
Counseling patients with central venous catheters who participate in activities involving exposure to domesticated animals is recommended
Introduction
Rhodococcus equi is an intracellular aerobic,
Gram-posi-tive, weakly acid-fast coccobacillus It has been
recog-nized as an animal pathogen since its original isolation
from foals with pneumonia in Sweden in 1923 [1]
Human infection with R equi is rare but is increasingly
encountered in patients with human immunodeficiency
virus (HIV) infection [2,3], and in solid organ transplant
recipients [1,4,5] In most of these cases, there has been
a history of contact with farm animals, contaminated
soil or manure, in which this organism is commonly
found [2] More than 80% of cases reported in the
Eng-lish medical literature have pulmonary involvement [5]
The remaining cases involve extrapulmonary sites such
as soft tissues, eyes and bone [5-7] Unfortunately, this
pathogen is still underestimated as a formidable
adver-sary in vulnerable patient populations and may be
discounted by physicians and microbiology laboratories
as a contaminant [2,5]
Central venous catheter-related bacteremia due to R equi has been rarely described in the literature and very few cases have been reported in cancer patients [8-10] Many cancer patients have a special form of central venous catheter known as a port It consists of a tun-neled subcutaneous reservoir with a catheter that con-nects to a vein (usually the subclavian or the superior vena cava)
We report the case of a 63-year-old woman without a history of organ transplantation or HIV infection, diag-nosed with recurrent endometrial carcinoma and muci-nous carcinoma of her appendix During the course of her treatment, she developed recurrent central venous catheter port line infections and septic shock due to
R equi, which was cultured from her central venous catheter tip She was ultimately successfully treated with removal of the catheter and a combination of antibiotics
* Correspondence: Zeina.nahleh@ttuhsc.edu
1
Department of Internal Medicine, TTUHSC-Paul L Foster School of Medicine,
4800 Alberta Avenue, El Paso, TX 79905, USA
Full list of author information is available at the end of the article
© 2011 Guerrero et al; licensee BioMed Central Ltd This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and
Trang 2Case Presentation
Our patient was a 63-year-old Caucasian woman She does
not smoke cigarettes or drink alcohol She measures
162.5 cm in height and weighs 66 kilograms She had no
significant family history She was initially diagnosed with
stage IIIA endometrial carcinoma for which she underwent
a hysterectomy and bilateral salpingo ophorectomy
fol-lowed by pelvic external beam radiation therapy Two
years later, she developed recurrent disease with
wide-spread peritoneal carcinomatosis An incidental mucinous
carcinoma of the appendix was also found during surgical
exploration A central venous catheter port was placed and
she received chemotherapy with 5-fluorouracil, leucovorin,
and later, irinotecan, capecitabine and oxaliplatin Her
dis-ease progressed despite multiple lines of chemotherapy
During the course of her cancer treatment, our patient also
developed a series of complications which included
tumor-related right ureteral obstruction requiring a nephrostomy
placement, a sigmoid-vaginal fistula necessitating a
colost-omy with reversion of the ureteral stent, small bowel
obstruction and ileostomy placement, short bowel
syn-drome and significant weight loss requiring total parenteral
nutrition Our patient recovered gradually and was able to
receive subsequent courses of chemotherapy consisting of
capecitabine, an oral chemotherapy agent classified as an
antimetabolite, and oxaliplatin, an intravenous
platinum-based chemotherapy agent classified as an alkylating agent
She developed predictable chemotherapy-related adverse
events including diarrhea and hand-foot syndrome, but
was able to continue her treatment intermittently She
started developing fever and tenderness at the site of her
central venous catheter Blood cultures were repeatedly
negative Our patient had not received antibiotics within
the eight weeks prior to this event She was not
neutrope-nic Laboratory results reflected a white blood cell (WBC)
count of 12,100 cells/μL, with 87% neutrophils Urine and
stool examination revealed no abnormal findings Liver
and renal function tests and a chest X-ray were normal
Blood cultures taken from both the central venous catheter
and peripheral vein were reported to have no growth after
96 hours incubation She received empiric vancomycin for
two weeks and all signs of infection, including fever,
resolved with normalization of WBC count to 7500 cells/
μL and 67% neutrophils However, four weeks later, she
was admitted to the intensive care unit with a septic shock
picture; she had fever, hypotension and tenderness at the
site of the central venous catheter, which was then
removed WBC count at this time was 18,400 cells/μL with
93% neutrophils A chest X-ray was negative for
pulmon-ary disease and sputum cultures revealed no microbial
growth She was empirically treated with intravenous
ticar-cillin/clavulanate, ciprofloxacin and vancomycin Cultures
from the catheter tip as well as blood cultures were
submitted for analysis Two days later, large, irregular mucoid colonies grew and were non-fermentative, distin-guishing them from diphtheria colonies Further incuba-tion grew characteristic salmon-colored colonies of R equi Microbiologic characteristics of the pathogen were as fol-lows: catalase and urease positive; oxidase, carbohydrate fermentation, mannitol, indole, and citric acid negative; equi factors positive The cultured organism was found to
be resistant in vitro to penicillins and susceptible to erythromycin, gentamicin, tobramycin, vancomycin, imipe-nem/cilastatin and rifampin Our patient’s antibiotic regi-men was modified to include the combination of a b-lactam antibiotic (imipenem/cilastatin) and a bactericidal antibiotic rifampin She received imipenem 500 mg intra-venously every 8 hrs for 14 days and rifampin 600 mg orally daily She was discharged on oral rifampin after reso-lution of her symptoms and two negative blood cultures were obtained She continued rifampin for twenty-one days and made a full recovery
Discussion
The first human case with R equi infection was reported in 1967 in a patient with autoimmune hepatitis who was undergoing treatment with prednisone and 6-mercaptopurine [11] He worked in a stockyard cleaning animal pens and subsequently developed lung and sub-cutaneous abscesses Since then, human cases of R equi infection have been described in immunocompromised patients In this subpopulation of patients, such infec-tions portend high mortality rates and usually require prolonged treatment with multiple antibiotics [2-8,12]
In contrast, immunocompetent patients respond well to shorter courses of antibiotics, usually with a single agent [13,14] With the exception of Antarctica, R equi has been identified in soils all over the world, in fresh and sea water and in animals including horses, cattle and wild birds [5] Human infection can be acquired through inhalation from the soil, inoculation into a wound or ingestion and passage through the alimentary tract [4,5] Other routes of acquisition include nosocomial spread, human colonization and person-to-person transmission [15] Exposure to domesticated animals such as horses and pigs has been reported in some cases of infection [16] Our patient may have potentially acquired R equi via exposure to contaminated horse fibers that she uses for her sculptures
In immunocompromised patients, pulmonary involve-ment is common, with necrotizing pneumonia being the most frequent presentation [4] Infection with this organism can be life-threatening and the required treat-ment is often lengthy In immunocompetent patients, pulmonary infections are also common and account for 42% of reported cases [14] Pulmonary infections have a
Trang 3relapsing and remitting course with intermittent
bacter-emia The onset of symptoms is usually insidious and
may occur over a span of days to weeks, with the
patient presenting with fever, non-productive cough,
dyspnea and pleuritic chest pain In some cases, weight
loss and hemoptysis, severe enough as to require blood
transfusions, have also been noted Chest radiographs
typically reveal pulmonary infiltrates with single or
mul-tiple lung segments, mainly in the upper lobes The
radiographic changes bear a striking resemblance to
those changes that occur with fungal or tubercular
infections Cavitations, pleural effusions or empyema
evolve over a two to four week period [4] Primary
extrapulmonary manifestations are unusual and occur
for the most part secondary to hematogenous
dissemi-nation Examples include subcutaneous nodules, brain
and renal abscess, lymphadenitis, endophthalmitis and
osteomyelitis [17]
Blood cultures are positive in more than one-half of
immunocompromised patients with R equi infection
com-pared to only 10% of normal hosts [18] Cultures of
R equi grow easily under aerobic conditions on
non-selec-tive media Large, irregular, highly mucoid colonies usually
grow optimally at 30°C and turn to a salmon-pink color
within 48 hours [18] Further incubation leads to release
of its red pigment leading to its characteristic
salmon-colored colonies It is non-fermentive which differentiates
Rhodococcus from Corynebacterium R equi is
catalase-and urease-positive, catalase-and oxidase-negative Biochemical
kits are now available which facilitate identification of
R equi Our patient had recurrent infections of the central
venous catheter which eventually led to its removal The
first set of blood cultures was reported as negative This
may have occurred, in part, due to the fact that infections
with R equi are missed because of incomplete or improper
identification of the organism [4,5] In addition, the
appearance of R equi as a Gram-positive, weakly acid-fast,
diphtheroid-like organism may lead to mistaken identity
with a component of the normal flora or a contaminant (a
diphtheroid, a micrococcus, or a Bacillus species) [2]
Therefore, a high degree of suspicion should be exercised
in susceptible patients Once R equi is cultured from a
sterile site, it should never be considered a contaminating
diphtheroid Septic shock in our patient resulted in part
from recurrent infections of the central venous catheter
Infections with R equi may be life-threatening due to
the toxicity of this organism, which is mediated by the
pre-sence of large plasmids that encode proteins necessary for
virulence inside the cell [19] This coding process ensures
the pathogen’s ability to persist and destroy macrophages
in the immunocompromised patient [20,21] Infection of
macrophages with R equi results in cytotoxicity,
particu-larly in high bacterial loads [22], and is regulated by
viru-lence-associated plasmids (VAP) [22,23] More recent
work suggests that the type of plasmid that is overcome by
a specific R equi strain determines its host specificity, as described by the plasmid-typing scheme known as TRA-VAP [23] TRATRA-VAP is an acronym that represents a poly-merase chain reaction (PCR) typing system for R equi in which three plasmid gene markers are evaluated The first marker is the traA which is found in the conserved conju-gal transfer machinery while vapA and vapB are found in two different plasmid subpopulations [23] In humans and
in healthy or afflicted animals with tuberculous-appearing lesions, isolated strains of R equi often possess a VAP cod-ing for a surface-localized 20-kDa protein, and has been referred to as“ vapB” due to its high homology to the vapA protein [19,24] VapA and vapB sequences are strongly related to each other (83.6% identity) [24] and so are the plasmids encoding them [25] Possession of certain vaps seems to be specific for strains infecting foals, pigs or cattle [19], but it is likely that R equi infections of humans are not determined by particular plasmids but by the basal and chromosomally determined pathogenic potential of R equi [26] Chromosomally encoded factors involved in R equi virulence have been reported [26,27] The mortality rate for R equi infection among immunocompetent patients is approximately 10%, compared with rates of 20-55% among immunocompromised patients, in particular, those with HIV [7] In humans, R equi typically resides in, and destroys, macrophages, making it difficult to eradicate especially in immunocompromised patients [12] This is exemplified in our case The organism persisted and colo-nized the central venous catheter after vancomycin ther-apy, despite therapeutic trough levels, with the organism remaining susceptible to vancomycin Another factor that may have led to therapeutic failure is the fact that this organism can inhibit macrophage phagosome-lysosome fusion and survives within the cell Therefore, vancomycin monotherapy may not be the ideal approach to the man-agement of central venous catheter bacteremia with R equi, despite its susceptibility to vancomycin Combination antimicrobial therapy using bactericidal and intracellular-active agents should be considered Also, prompt removal
of the infected central venous catheter is necessary for adequate infection control, as was the case in our patient Therapeutic failure may also occur following a deficient course of treatment Based on similar experiences with dif-ficult-to-treat organisms like Mycobacterium tuberculosis, and on the fact that distant relapses of rhodococcus infec-tion are common, prolonged therapy is recommended [28] Although there is no consensus on the optimal dura-tion or regimen of antibiotic treatment, the use of combi-nation therapy may decrease the risk of developing resistance during therapy, which has been described with penicillin and otherb-lactam antibiotics A carbapenem and a glycopeptide, such as meropenem and vancomycin, are good choices [29] The combination of macrolides and
Trang 4rifampin can also be considered [30] Other combinations
may include a macrolide antibiotic such as erythromycin
along with rifampin, vancomycin, fluoroquinolones,
ami-noglycosides or broad spectrumb-lactam antibiotics such
as imipenem/cilastatin [28-32] After initial improvement,
the patient can be treated with an oral regimen that could
include combinations of quinolones, tetracycline,
macro-lides, and rifampin
The optimal duration of treatment is unknown Our
patient was successfully treated with a combination of
imipenem/cilastatin and rifampin for 14 days, and then
continued oral rifampin for 21 days Due to the
intracel-lular nature of the pathogen, which concentrates in
gran-ulocytes and macrophages [31], a prolonged treatment
course is advised in immunocompromised patients due
to frequent relapses following abbreviated treatment
courses Monotherapy with penicillin and most other
b-lactam antibiotics should be avoided even if R equi is
initially sensitive, sinceb-lactam resistance may develop
during therapy [2] Also, the minimal inhibitory
concen-trations of rifampin and erythromycin for R equi strains
isolated within the last 10 years have been rising [33] and
the emergence of resistant strains to different antibiotics
have been reported [34] These findings highlight the
need for strategies other than antibiotic therapy to
pre-vent or treat R equi infections, such as applications of
gallium nitrate and vaccination methods [35-41] In the
case of patients taking immunosuppressive therapy
fol-lowing organ transplants, the challenge in the treatment
of R equi is the possible interactions of common
combi-nation therapy like macrolide antibiotic and rifampin
with immunosuppressive agents like tacrolimus or
cyclosporine, which are routinely used in these patients
In one case report of a heart transplant patient on
immu-nosuppressive therapy, the excellent response to
treat-ment of R equi occurred following the treattreat-ment with a
combination of minocycline and a fluoroquinolone [42]
Overall there is no agreement on the treatment of R equi
infections in transplant recipients receiving
immunosup-pressive therapy A review of the literature and scattered
case reports describes different combinations that may
prove beneficial in organ transplant recipients, such as a
case of a kidney transplant patient who had good results
using the combination of carbapenem and teicoplanin
[43] Synergistic combinations of medications are also
key, as was demonstrated in human isolates determined
by fractional inhibitory concentration indices Such
combinations included: rifampin-minocycline,
erythro-mycin-minocycline, rifampin-erythromycin and
imipe-nem-amikacin [44] Weinstock and Brown [45] proposed
an algorithm for the management of R equi infections in
immunocompromised hosts They recommended an
initial treatment with two agents to avoid development of
resistance Vancomycin, carbapenems, quinolones,
erythromycin, and rifampin are reasonable first choices Careful scrutiny of all other medications is mandatory if drug interactions are to be avoided Later adjustment of therapy based on susceptibility data is recommended After two weeks of intravenous therapy and attendant clinical improvement, oral antibiotics may be substituted with rifampin, erythromycin, or ciprofloxacin [45] Six months or more of therapy may be required for lung, bone and joint, and cerebral infections [45] Novel diag-nostic techniques using specific quantitative PCR should
be further explored [46,47]
Conclusion
Human infection with R equi should be considered when evaluating immunocompromised patients with a central venous catheter and fever in the setting of expo-sure to farm animals Microbiologists should be familiar with the growth requirements and biochemical proper-ties of this organism If the pathogen is suspected and identified, the tunneled central venous catheter should
be removed to prevent recurrence Due to the fact that virulent strains of R equi are resistant to phagocytosis and intracellular killing by macrophages, patients should receive a combination of bactericidal and intracellular-active agents that will penetrate cells, such as rifampin and macrolide antibiotics A prolonged course of an oral antibiotic following initial intravenous therapy has been suggested in the light of frequent relapses with shorter courses Counseling should be provided to immunocom-promised patients inclined to participate in activities involving exposure to domesticated animals or their products
Consent
Written informed consent was obtained from the patient for publication of this case report A copy of the written consent is available for review by the Editor-in-Chief of this journal
Author details
1 Department of Internal Medicine, TTUHSC-Paul L Foster School of Medicine,
4800 Alberta Avenue, El Paso, TX 79905, USA 2 Department of Internal Medicine, Wayne State University/Detroit Medical Center, 4100 John R, 4HWCRC, Detroit, MI 48201, USA.
Authors ’ contributions
ZN developed the manuscript idea, gathered case details, performed the history, physical exam and the treatment of the patient, and co-wrote and edited the manuscript RG was a major contributor in writing the manuscript AB reviewed the literature and contributed to writing the manuscript All authors read and approved the final manuscript.
Competing interests The authors declare that they have no competing interests.
Received: 3 December 2009 Accepted: 9 August 2011 Published: 9 August 2011
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doi:10.1186/1752-1947-5-358
Cite this article as: Guerrero et al.: Rhodococcus equi venous catheter
infection: a case report and review of the literature Journal of Medical
Case Reports 2011 5:358.
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